A major drawback of gene silencing techniques such as RNA interference is the occurrence of off-target effects. Off-target effects occur when a gene-silencing agent has an effect on a gene product to which it is not targeted, and is therefore unwanted. Off-target effects loom as one of the main hurdles for developing gene silencing therapeutics.
One method to reduce off-target effects is to intelligently design the structure of the gene silencing agent to avoid effects on genes other than the desired target. In some cases, the gene silencing agents could be pooled so that the concentration of agents having a particular off-target effect would be reduced. In other cases, the gene silencing agent could be chemically modified to avoid off-targets effects. These conventional methods have been able to reduce off-target effects, however, they can be difficult to carry out.
What is needed are gene silencing agents with reduced off target effects.
There is a long-standing need for methods and compositions for therapeutic oligomers that operate via RNA interference, which avoid or reduce off target effects.